Metabolic associated fatty liver disease （MAFLD） is a common chronic liver disease worldwide， and timely and precise intervention can delay disease progression and significantly reduce the risk of serious complications such as liver fibrosis， liver cirrhosis， and liver cancer. Although traditional liver biopsy combined with metabolic markers is the gold standard， it may cause complications such as pain and bleeding as an invasive examination， which has promoted scientific research to shift its focus to the construction of noninvasive assessment systems. In recent years， noninvasive diagnostic technologies based on multi-dimensional detection strategies have been continuously updated， including serological models， imaging techniques， and clinical algorithms. This article systematically reviews the screening methods for MAFLD during the fibrotic stages F1—F3， especially deep learning models based on artificial intelligence， in order to provide ideas for the early screening of MAFLD， as well as a scientific reference for optimizing disease management strategies.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

Objective: To elucidate the biological basis of traditional Chinese medicine (TCM) syndromes from the perspective of “same syndrome, different diseases” in patients with chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC), thereby providing a complementary approach for the diagnosis and treatment of chronic liver diseases (CLD). Methods: To investigate the dynamic characteristics of TCM syndromes in CLD, transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) was performed from patients with CHB, LC, or HCC presenting with three TCM syndromes: liver gallbladder dampness heat syndrome (LGDHS), liver depression spleen deficiency syndrome (LDSDS), and liver kidney Yin deficiency syndrome (LKYDS). These participants were recruited at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between August 1, 2018 and December 31, 2021. Differentially expressed genes (DEGs) were identified using the random variance model (RVM) F test with false discovery rate (FDR) correction. Principal component analysis (PCA) and unsupervised hierarchical clustering were applied to visualize sample grouping. Dynamic network biomarkers (DNB) analysis was employed to detect critical transition stages during syndrome evolution, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to characterize the functional roles and pathway involvement of the DNB members. Random forest (RF) analysis and the area under the receiver operating characteristic (ROC) curves (AUC) were used to rank the importance of candidate genes. External validation was performed using microarray data from an independent CLD cohort (GSE89377) and RNA-seq data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. Additionally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed on an independent cohort of LC patients to validate the expression levels of the candidate genes. Results: The study included a total of 132 participants. DNB analysis identified LDSDS stage as a critical tipping point during TCM syndrome evolution across CHB, LC, and HCC. The phosphoinositide 3-kinase/protein kinase B (PI3K-AKT) signaling pathway was consistently enriched in the DNB analysis across all three types of CLD, suggesting its potential involvement in the critical transition of TCM syndromes. Among the 24 core DNB members of the PI3K-AKT pathway, four genes—integrin subunit beta 1 (ITGB1), collagen type IV alpha 1 chain (COL4A1), collagen type IV alpha 2 chain (COL4A2), and DNA damage inducible transcript 3 (DDIT3)—were identified by RF analysis (Gini score > 1) and ROC analysis. ROC analysis demonstrated high discriminative ability for distinguishing LGDHS from LKYDS in CHB patients, with AUC of 0.7891 for ITGB1, 0.7070 for COL4A1, 0.7148 for COL4A2, and 0.8945 for DDIT3. In the independent CLD cohort (GSE89377), all four genes showed significant stepwise upregulation from normal to CHB, LC, and HCC (all P < 0.05). In the TCGA-LIHC dataset, their expression progressively increased with tumor stage. RT-qPCR validation in an independent LC cohort (30 LGDHS vs. 30 LKYDS) confirmed that ITGB1, COL4A2, and DDIT3 were significantly upregulated in LKYDS compared with LGDHS (P = 0.0152, 0.0186, and 0.0247, respectively), whereas COL4A1 showed a non-significant upward trend (P = 0.1201). Conclusion This study introduces a novel approach to understanding the molecular features underlying TCM syndrome evolution in CLD. The PI3K-AKT pathway and four identified genes (ITGB1, COL4A1, COL4A2, and DDIT3) play crucial roles in the transition from excess (LGDHS) to deficiency (LKYDS) via the critical LDSDS stage. These findings offer potential quantitative biomarkers and therapeutic targets for TCM syndrome differentiation and may help arrest syndrome progression in CLD.

Background: Aspiration pneumonia (AP), which can be caused by gastric content inhalation into the lower airways, causes acute lung injury (ALI) through complex mechanisms, including inflammation, oxidative stress, and apoptosis. Here, we evaluated the efficacy of exosomes derived from human placental mesenchymal stem cells (hpMSCs) in mitigating ALI in a murine model of AP. We also investigated the role of hsa-let-7i-5p, the most abundant miRNA in hpMSC-derived exosomes, in this respect. Methods: Adult male C57BL/6 mouse AP models were administered hpMSC-derived exosomes (APExo group) or phosphate-buffered saline (AP group) intra-tracheally. After 48 h, the mice were euthanized and evaluated. The effects of hsa-let-7i-5p were assessed by specific inhibition or overexpression. Results: Compared with the APExo group, the AP group exhibited significantly greater ALI, as evidenced by histological damage, increased lung injury scores, impaired lung function, increased leukocyte infiltration, and elevated tissue edema (all P < 0.05). The untreated AP group also showed more inflammation, characterized by nuclear factor-κB upregulation, macrophage M1 polarization, and cytokine level elevation (tumor necrosis factor-α, interleukin-1β, and interleukin-6), as well as increased oxidation and activation of the apoptosis pathway (all P < 0.05). Notably, the therapeutic effects of hpMSC-derived exosomes were compromised by specific inhibition of hsa-let-7i-5p. Furthermore, engineered exosomes derived from genetically modified RAW264.7 overexpressing hsa-let-7i-5p demonstrated therapeutic effects against AP similar to those obtained with hpMSC-derived exosomes. Conclusions In a murine AP model, intra-tracheal administration of hpMSC-derived exosomes has ALI-mitigating effects, involving inflammation, oxidation, and apoptosis modulation, with hsa-let-7i-5p playing a pivotal mediating role.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Introduction: Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder that significantly affects adolescent girls, particularly those with overweight or obesity. However, data examining the determinants and metabolic profiles of PCOS among adolescents with overweight and obesity remain limited, especially in Malaysia. This protocol describes a case-control study investigating the cardiometabolic, dietary, and psychosocial determinants of PCOS among adolescents with overweight and obesity. Methodology: This study is designed as a case-control study involving adolescent girls aged 13–16 years with a body mass index z-score >+1 standard deviation. Cases are defined as adolescent girls with a confirmed diagnosis of PCOS based on the recommendations of the 2017 International Consortium of Paediatric Endocrinology (ICPE), while controls are those who do not meet the diagnostic criteria for PCOS. A total sample size of 440 participants is required. Participants will be recruited from 22 secondary schools selected from a list of schools in Kuala Lumpur. Data on sociodemographic characteristics, psychosocial health, physical activity, and dietary intake will be collected using structured questionnaires. Blood samples will be obtained and analyzed for diagnostic testing (free testosterone), exclusion tests (thyroid-stimulating hormone, folliclestimulating hormone, luteinizing hormone, estradiol, prolactin, and dehydroepiandrosterone sulfate), and biochemical parameters (liver function tests, lipid profile, hemoglobin A1c, fasting glucose, fasting insulin, and inflammatory markers). Results: The study is expected to generate comprehensive data on the cardiometabolic, dietary, and psychosocial determinants of PCOS among adolescents with overweight and obesity. The findings will inform early screening strategies and targeted interventions aimed at reducing long-term reproductive and cardiometabolic complications. Conclusion This protocol outlines a structured approach to investigating PCOS in adolescence and addresses current gaps in early identification and risk stratification among highrisk populations.
Adolescent ; Humans ; Case-Control Studies ; Overweight ; Polycystic Ovary Syndrome ; Obesity

Introduction: ISPAD guidelines recommend continuous glucose monitoring (CGM) as the standard of care for paediatric type 1 diabetes (T1DM). However, a “real-world” adoption gap persists, particularly in resource-limited settings. The Introductions of the study were to evaluate CGM adoption prevalence, identify documented barriers, and compare glycemic outcomes between active and non-active users. Methodology: This retrospective review analyzed electronic medical records (EMR) of 125 paediatric T1DM patients at Hospital Putrajaya (2025). Data included CGM status, insulin delivery method, and documented barriers. Independent T-tests compared mean hemoglobin A1c (HbA1c) between groups, and multivariable logistic regression identified independent predictors of adoption. Results: Cohort mean age was 11.8 ± 3.8 years. Active CGM users were 32.8% (n = 41), of whom 29.3% (n = 12) utilized predominantly automated insulin delivery (AID) systems. The remaining 67.2% (n = 84) were classified as non-active users, comprising both never-users and ex-users (discontinued use). Active users achieved significantly lower mean HbA1c than non-active users (8.73% vs 9.86%; p <0.001), with no significant difference in rates of DKA (p = 0.564) or severe hypoglycemia (p = 0.250). Among never-users, 42.9% lacked documented technology counselling (p = 0.001). Multivariable analysis identified funding source as the sole independent predictor of CGM adoption (adjusted OR = 7.76, p <0.001). While the primary documented barrier was financial (31.0%), a lack of documented barriers was noted in 61.9% of non-active users. Conclusion A substantial technology gap exists, primarily driven by financial access rather than clinical demographics. The difference of 1.13% in HbA1c between groups underscores the need to address financial setbacks to improve technology access in Malaysia and prevent diabetes complications.
Child ; Blood Glucose ; Blood Glucose Self-Monitoring ; Continuous Glucose Monitoring ; Diabetes Mellitus, Type 1